ERK及其磷酸化在晚期前列腺癌組織中的表達(dá)及意義
發(fā)布時(shí)間：2018-08-20 12:26
【摘要】：目的:前列腺癌在55歲以上的男性人群中的發(fā)病率較高,且隨著年齡的增長(zhǎng)而升高。近年來(lái),前列腺癌的發(fā)病率已躍居男性惡性腫瘤第二位,在我國(guó),其發(fā)病率也逐年增高,占男性惡性腫瘤第三位,病死率僅次于肺癌。絲裂原活化蛋白激酶(MAPK)是細(xì)胞內(nèi)信號(hào)傳遞途徑的共同通道及匯聚點(diǎn),細(xì)胞外信號(hào)調(diào)節(jié)激酶(ERK)是其家族成員之一。大量研究表明在惡性腫瘤中均存在ERK信號(hào)轉(zhuǎn)導(dǎo)通路,該通路在惡性腫瘤中有至關(guān)重要的作用,在前列腺癌中也存在著該通路,但目前,國(guó)內(nèi)外對(duì)ERK信號(hào)轉(zhuǎn)導(dǎo)通路在前列腺癌中的研究?jī)A向于腫瘤的分期、分級(jí),對(duì)前列腺癌患者的生存預(yù)后研究較為缺乏,本次研究不僅對(duì)前列腺癌的侵襲力、PSA水平做了研究,而且對(duì)前列腺癌患者的生存預(yù)后做了相關(guān)性分析,為ERK信號(hào)轉(zhuǎn)導(dǎo)通路影響前列腺癌患者的預(yù)后提供了相關(guān)的臨床數(shù)據(jù)。本次研究主要探討細(xì)胞外信號(hào)調(diào)節(jié)激酶(ERK)及其磷酸化狀態(tài)(p-ERK)在前列腺增生組織和晚期前列腺癌組織中的表達(dá),以及能否作為判斷晚期前列腺癌預(yù)后的標(biāo)志物。方法:選取大連醫(yī)科大學(xué)附屬第一醫(yī)院2008年10月到2011年2月具有完整病例資料的晚期前列腺癌組織40例及前列腺增生組織20例,其中晚期前列腺癌組織40例,均為T3/T4/Nx-1Mx期,因尿路梗阻均行經(jīng)尿道前列腺電切術(shù)+雙側(cè)睪丸切除術(shù),所有患者術(shù)后均行規(guī)律內(nèi)分泌治療,且排除其他腫瘤病史;前列腺增生組織20例,均因尿路梗阻行經(jīng)尿道前列腺電切術(shù)�；颊吣挲g在58-86歲之間,平均年齡73歲,手術(shù)切除組織標(biāo)本均經(jīng)10%甲醛固定24小時(shí)后,做常規(guī)石蠟包埋處理。應(yīng)用免疫組織化學(xué)(Envision)法檢測(cè)前列腺增生組織(benign prostatic hyperplasia,BPH)及晚期前列腺癌(PCa)組織中ERK1/2及其磷酸化狀態(tài)(p-ERK1/2)的表達(dá),并分析其與晚期前列腺癌轉(zhuǎn)移(侵襲力)、Gleason評(píng)分、PSA水平以及生存時(shí)間的關(guān)系。結(jié)果:(1)ERK1/2的表達(dá):在前列腺增生組織中陽(yáng)性表達(dá)率為55.0%,在晚期前列腺癌組織中陽(yáng)性表達(dá)率為82.5%,具有顯著性差異(P0.05);在晚期前列腺癌轉(zhuǎn)移組與未轉(zhuǎn)移組中陽(yáng)性表達(dá)率分別為84.2%、80.9%,無(wú)顯著性差異(P0.05);在Gleason評(píng)分7分與Gleason評(píng)分≤7分中的陽(yáng)性表達(dá)率分別為91.3%、70.6%,無(wú)顯著性差異(P0.05);在PSA20ng/ml與PSA≤20ng/ml中的陽(yáng)性表達(dá)率分別為87.5%、62.5%,無(wú)顯著性差異(P0.05);在生存時(shí)間5年與生存時(shí)間≤ 5年中的陽(yáng)性表達(dá)率分別為84.2%、80.9%,無(wú)顯著性差異(P0.05);(2)p-ERK1/2的表達(dá):前列腺增生組織中陽(yáng)性表達(dá)率為35.0%,晚期前列腺癌組織中陽(yáng)性表達(dá)率為75.0%,有顯著性差異(P0.05);在Gleason評(píng)分7分與Gleason評(píng)分≤7分中的陽(yáng)性表達(dá)率分別為73.9%、76.5%,無(wú)顯著性差異(P0.05);在PSA20ng/ml與PSA≤20ng/ml中的陽(yáng)性表達(dá)率分別為78.1%、62.5%,無(wú)顯著性差異(P0.05);在晚期前列腺癌轉(zhuǎn)移組和未轉(zhuǎn)移組中陽(yáng)性表達(dá)率分別為:61.9%、89.5%,有顯著性差異(P0.05);在生存時(shí)間5年與生存時(shí)間≤5年組中陽(yáng)性表達(dá)率分別為:57.9%、90.5%,有顯著性差異(P0.05)。結(jié)論:ERK1/2、p-ERK1/2在晚期前列腺癌組織中高表達(dá),ERK1/2磷酸化與晚期前列腺癌侵襲力(轉(zhuǎn)移)及預(yù)后有關(guān)。
[Abstract]:Objective: The incidence of prostate cancer in men over 55 years old is higher, and it increases with age. In recent years, the incidence of prostate cancer has jumped to the second place in male malignant tumors. In China, the incidence of prostate cancer has also increased year by year, accounting for the third place in male malignant tumors, mortality is only second to lung cancer. Mitogen-activated protein kinase (MA) Extracellular signal-regulated kinase (ERK) is one of the family members of PK, which is the common pathway and convergence point of intracellular signal transduction pathway. A large number of studies have shown that ERK signal transduction pathway exists in malignant tumors. This pathway plays an important role in malignant tumors and also exists in prostate cancer. However, at present, it is widely used in prostate cancer at home and abroad. The research of ERK signal transduction pathway in prostate cancer tends to staging and grading of tumor, and the study of survival and prognosis of prostate cancer patients is scarce. This study not only studied the invasiveness and PSA level of prostate cancer, but also analyzed the correlation between the survival and prognosis of prostate cancer patients, and affected the ERK signal transduction pathway. This study was designed to investigate the expression of extracellular signal-regulated kinase (ERK) and its phosphorylated state (p-ERK) in prostate hyperplasia and advanced prostate cancer, and whether they can be used as prognostic markers of advanced prostate cancer. From October 2008 to February 2011, the First Affiliated Hospital had complete data of 40 cases of advanced prostate cancer and 20 cases of benign prostatic hyperplasia. Among them, 40 cases of advanced prostate cancer were of stage T3/T4/Nx-1Mx. All patients underwent transurethral resection of prostate and bilateral orchiectomy due to urinary obstruction. 20 cases of benign prostatic hyperplasia were treated by transurethral resection of prostate due to urinary tract obstruction. The patients were aged from 58 to 86 years, with an average age of 73 years. The expression of ERK1/2 and its phosphorylated state (p-ERK1/2) in benign prostatic hyperplasia (BPH) and advanced prostate cancer (PCa) tissues was analyzed. The relationship between the expression of ERK1/2 and metastasis (invasiveness), Gleason score, PSA level and survival time of advanced prostate cancer was analyzed. The positive expression rate was 82.5% in advanced prostate cancer (P 0.05), 84.2% in metastatic group and 80.9% in non-metastatic group (P 0.05), 91.3% in Gleason score 7 and 70.6% in Gleason score < 7, respectively. The positive expression rates of PSA20ng/ml and PSA < 20ng/ml were 87.5% and 62.5%, respectively, with no significant difference (P 0.05); the positive expression rates of PSA20ng/ml and PSA < 20ng/ml were 84.2% and 80.9% respectively, with no significant difference (P 0.05); (2) the expression of p-ERK1/2 in prostate hyperplasia tissues was 35.0% and in advanced prostatic hyperplasia tissues. The positive expression rate in adenocarcinoma tissues was 75.0% (P 0.05), 73.9% in Gleason score 7 and 76.5% in Gleason score < 7, respectively, with no significant difference (P 0.05), 78.1% in PSA20ng/ml and 62.5% in PSA < 20ng/ml, respectively, without significant difference (P 0.05). The positive expression rates of ERK1/2 and p-ERK1/2 were 61.9% and 89.5% respectively in the metastatic group and the non-metastatic group, with significant difference (P 0.05), and 57.9% and 90.5% respectively in the 5-year survival group and the 5-year survival group (P 0.05). Impact (metastasis) is associated with prognosis.
【學(xué)位授予單位】：大連醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R737.25
，
本文編號(hào)：2193603
[Abstract]:Objective: The incidence of prostate cancer in men over 55 years old is higher, and it increases with age. In recent years, the incidence of prostate cancer has jumped to the second place in male malignant tumors. In China, the incidence of prostate cancer has also increased year by year, accounting for the third place in male malignant tumors, mortality is only second to lung cancer. Mitogen-activated protein kinase (MA) Extracellular signal-regulated kinase (ERK) is one of the family members of PK, which is the common pathway and convergence point of intracellular signal transduction pathway. A large number of studies have shown that ERK signal transduction pathway exists in malignant tumors. This pathway plays an important role in malignant tumors and also exists in prostate cancer. However, at present, it is widely used in prostate cancer at home and abroad. The research of ERK signal transduction pathway in prostate cancer tends to staging and grading of tumor, and the study of survival and prognosis of prostate cancer patients is scarce. This study not only studied the invasiveness and PSA level of prostate cancer, but also analyzed the correlation between the survival and prognosis of prostate cancer patients, and affected the ERK signal transduction pathway. This study was designed to investigate the expression of extracellular signal-regulated kinase (ERK) and its phosphorylated state (p-ERK) in prostate hyperplasia and advanced prostate cancer, and whether they can be used as prognostic markers of advanced prostate cancer. From October 2008 to February 2011, the First Affiliated Hospital had complete data of 40 cases of advanced prostate cancer and 20 cases of benign prostatic hyperplasia. Among them, 40 cases of advanced prostate cancer were of stage T3/T4/Nx-1Mx. All patients underwent transurethral resection of prostate and bilateral orchiectomy due to urinary obstruction. 20 cases of benign prostatic hyperplasia were treated by transurethral resection of prostate due to urinary tract obstruction. The patients were aged from 58 to 86 years, with an average age of 73 years. The expression of ERK1/2 and its phosphorylated state (p-ERK1/2) in benign prostatic hyperplasia (BPH) and advanced prostate cancer (PCa) tissues was analyzed. The relationship between the expression of ERK1/2 and metastasis (invasiveness), Gleason score, PSA level and survival time of advanced prostate cancer was analyzed. The positive expression rate was 82.5% in advanced prostate cancer (P 0.05), 84.2% in metastatic group and 80.9% in non-metastatic group (P 0.05), 91.3% in Gleason score 7 and 70.6% in Gleason score < 7, respectively. The positive expression rates of PSA20ng/ml and PSA < 20ng/ml were 87.5% and 62.5%, respectively, with no significant difference (P 0.05); the positive expression rates of PSA20ng/ml and PSA < 20ng/ml were 84.2% and 80.9% respectively, with no significant difference (P 0.05); (2) the expression of p-ERK1/2 in prostate hyperplasia tissues was 35.0% and in advanced prostatic hyperplasia tissues. The positive expression rate in adenocarcinoma tissues was 75.0% (P 0.05), 73.9% in Gleason score 7 and 76.5% in Gleason score < 7, respectively, with no significant difference (P 0.05), 78.1% in PSA20ng/ml and 62.5% in PSA < 20ng/ml, respectively, without significant difference (P 0.05). The positive expression rates of ERK1/2 and p-ERK1/2 were 61.9% and 89.5% respectively in the metastatic group and the non-metastatic group, with significant difference (P 0.05), and 57.9% and 90.5% respectively in the 5-year survival group and the 5-year survival group (P 0.05). Impact (metastasis) is associated with prognosis.
【學(xué)位授予單位】：大連醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R737.25
，
本文編號(hào)：2193603
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